Code-ICH: A New Paradigm for Emergency Intervention.

PURPOSE OF REVIEW: Intracerebral hemorrhage (ICH) is the most devastating type of stroke, causing widespread disability and mortality. Unfortunately, the acute care of ICH has lagged behind that of ischemic stroke. There is an increasing body of evidence supporting the importance of early interventions including aggressive control of blood pressure and reversal of anticoagulation in the initial minutes to hours of presentation. This review highlights scientific evidence behind a new paradigm to care for these patients called Code-ICH. RECENT FINDINGS: While numerous trials aimed at decreasing hematoma expansion through single interventions had failed to show statistically significant effects on primary outcomes, time-sensitive, multifaceted, bundled care approaches have recently shown substantial promise in improving functional outcomes in patients with ICH. The concept of Code-ICH can serve as a structural platform for the practice of acute care neurology to continuously measure its performance, reflect on best practices, advance care, and address disparities.

Evaluation of soil nutrients and berry quality characteristics of Cabernet Gernischet (Vitis vinifera L.) vineyards in the eastern foothills of the Helan Mountains, China.

Soil is the basis of the existence of fruit tree and soil nutrients plays a crucial role in plant growth and berry quality. To investigate the characteristics and interrelationships between soil nutrients and berry quality in Cabernet Gernischet vineyards, this study focused on seven representative vineyards in the eastern foothills of the Helan Mountains. Fifteen soil physicochemical factors and 10 berry quality factors were measured, followed by variation analysis, correlation analysis, multiple linear regression (MLR), partial-least squares regression (PLSR), principal component analysis (PCA), and systematic cluster analysis. We identified the main soil nutrient indicators influencing berry quality and developed linear regression equations. Utilizing PCA, a comprehensive evaluation model for berry quality was constructed, which enabled the calculation and ranking of integrated berry quality scores. The results indicated that soil nutrients in the vineyards of the eastern foothills of the Helan Mountains are relatively deficient and alkaline. The coefficient of variation for soil nutrient factors ranged from 3.19 to 118.08% and for berry quality factors 2.41-26.37%. Correlation analysis revealed varying degrees of correlation between soil nutrient indicators and fruit quality indicators. PCA extracted four principal components with a cumulative contribution rate of 91.506%. Based on the scores of these components and their corresponding weights, a comprehensive model for evaluating the quality of Cabernet Gernischet berries was established. The vineyards were ranked from the highest to the lowest combined scores as Zhenbeibu (ZBB), Yuquanying (YQY), Dawukou (DWK), Beihaizi (BHZ), Shuxin (SX), Huangyangtan (HYT), and Hongde (HD). These findings provide insights into soil nutrient management and comprehensive quality assessment of vineyards in the eastern foothills of the Helan Mountains. In conclusion, this study offers a theoretical foundation for vineyard managers to enhance grape berries quality through soil nutrient management. This will aid in the diagnosis of vineyard soil nutrition and the efficient use of fertilizers, with critical practical and theoretical implications for the meticulous management of vineyards and the production of high-quality wines.

Genetically proxied appendicular lean mass and stroke risk: A two-step mendelian randomization study.

BACKGROUND AND PURPOSE: Prior observational studies have suggested a strong correlation between sarcopenia and stroke, but the causal link between them remains uncertain. This study aims to investigate the associations between genetically predicted sarcopenia-related traits and stroke using a two-step Mendelian randomization (MR) approach. METHODS: Genome-wide association study (GWAS) summary data for sarcopenia-related traits were acquired from the UK Biobank. Genetic associations for ischemic stroke (IS) and its subtypes were selected from the MEGASTROKE consortium comprising European ancestry participants. GWAS summary data for cerebral hemorrhage were obtained from the FinnGen consortium, including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). MR estimates were calculated using the inverse-variance weighted (IVW) method. The robustness of results was assessed for heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs). RESULTS: Higher appendicular lean mass (ALM) exhibited a potential causal association with a reduced incidence of large artery atherosclerosis (LAA) (odds ratio [OR] = 0.81, 95% confidence interval [CI]:0.71-0.93; P = 0.003) and small vessel disease (SVD) (OR = 0.83, 95% CI:0.74-0.94; P = 0.002). The associations of ALM with IS and ICH were compromised after adjusting for body fat and physical activity with multivariable MR. Two-step MR mediation analysis explored 33 candidate mediators, among which hypertension and SBP accounted for more than 10% of the mediation proportion in the relationship between ALM and stroke and its subtypes. CONCLUSION: Our research findings indicate that lower ALM is associated with a increased risk of stroke . It is necessary to explore the specific protective mechanisms of higher ALM for preventing stroke occurrence.

Numerical simulation and in vitro experimental study of the hemodynamic performance of vena cava filters with helical forms.

Inferior vena cava filter (IVCF) implantation is a common method of thrombus capture. By implanting a filter in the inferior vena cava (IVC), microemboli can be effectively blocked from entering the pulmonary circulation, thereby avoiding acute pulmonary embolism (PE). Inspired by the helical flow effect in the human arterial system, we propose a helical retrievable IVCF, which, due to the presence of a helical structure inducing a helical flow pattern of blood in the region near the IVCF, can effectively avoid the deposition of microemboli in the vicinity of the IVCF while promoting the cleavage of the captured thrombus clot. It also reduces the risk of IVCF dislodging and slipping in the vessel because its shape expands in the radial direction, allowing its distal end to fit closely to the IVC wall, and because its contact structure with the inner IVC wall is curved, increasing the contact area and reducing the risk of the vessel wall being punctured by the IVCF support structure. We used ANSYS 2023 software to conduct unidirectional fluid-structure coupling simulation of four different forms of IVCF, combined with microthrombus capture experiments in vitro, to explore the impact of these four forms of IVCF on blood flow patterns and to evaluate the risk of IVCF perforation and IVCF dislocation. It can be seen from the numerical simulation results that the helical structure does have the function of inducing blood flow to undergo helical flow dynamics, and the increase in wall shear stress (WSS) brought about by this function can improve the situation of thrombosis accumulation to a certain extent. Meanwhile, the placement of IVCF will change the flow state of blood flow and lead to the deformation of blood vessels. In in vitro experiments, we found that the density of the helical support rod is a key factor affecting the thrombus trapping efficiency, and in addition, the contact area between the IVCF and the vessel wall has a major influence on the risk of IVCF displacement.

Electronic cooling and energy harvesting using ferroelectric polymer composites.

Thermal management emerges as a grand challenge of next-generation electronics. Efforts to develop compact, solid-state cooling devices have led to the exploration of the electrocaloric effect of ferroelectric polymers. Despite recent advances, the applications of electrocaloric polymers on electronics operating at elevated temperatures remain essentially unexplored. Here, we report that the ferroelectric polymer composite composed of highly-polarized barium strontium titanate nanofibers and electron-accepting [6,6] phenyl-C61-butyric acid methyl ester retains fast electrocaloric responses and stable cyclability at elevated temperatures. We demonstrate the effectiveness of electrocaloric cooling in a polymer composite for a pyroelectric energy harvesting device. The device utilizes a simulated central processing unit (CPU) as the heat source. Our results show that the device remains operational even when the CPU is overheated. Furthermore, we show that the composite functions simultaneously as a pyroelectric energy converter to harvest thermal energy from an overheated chip into electricity in the electrocaloric process. This work suggests a distinct approach for overheating protection and recycling waste heat of microelectronics.

Rosiglitazone attenuates Acute Kidney Injury from hepatic ischemia-reperfusion in mice by inhibiting arachidonic acid metabolism through the PPAR-γ/NF-κB pathway.

BACKGROUND: Acute Kidney Injury (AKI), a prevalent complication of Liver Transplantation (LT) that occurs during the perioperative period has been established to profoundly impact the prognosis of transplant recipients. This study aimed to investigate the mechanism of the hepatic IRI-induced AKI and to identify potential therapeutic targets for treating this condition and improving the prognosis of LT patients. METHODS: An integrated transcriptomics and proteomics approach was employed to investigate transcriptional and proteomic alterations in hepatic IRI-induced AKI and the hypoxia-reoxygenation (H/R) model using TCMK-1 cells and the hepatic IRI-induced AKI mouse model using male C57BL/6 J mice were employed to elucidate the underlying mechanisms. Hematoxylin-eosin staining, reverse transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot were used to assess the effect of Rosiglitazone (RGZ) on hepatic IRI-induced AKI in vitro and in vivo. RESULTS: According to the results, 322 genes and 128 proteins were differentially expressed between the sham and AKI groups. Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway analyses revealed significant enrichment in pathways related to amino acid and lipid metabolism. Additionally, the Protein-Protein Interaction (PPI) network analysis of the kidney tissues obtained from a hepatic IRI-induced AKI mouse model highlighted arachidonic acid metabolism as the most prominent pathway. Animal and cellular analyses further revealed that RGZ, a PPAR-γ agonist, could inhibit the expression of the PPAR-γ/NF-κB signaling pathway-associated proteins in in vitro and in vivo. CONCLUSIONS: These findings collectively suggest that RGZ ameliorates hepatic IRI-induced AKI via PPAR-γ/NF-κB signaling pathway modulation, highlighting PPAR-γ as a crucial therapeutic target for AKI prevention post-LT.

Prevalence of sexual dysfunction in health care workers: a systematic review and meta-analysis.

INTRODUCTION: Health care workers represent a substantial demographic whose welfare and work efficiency are crucial to public health and societal well-being. However, the prevalence of sexual dysfunction within this group is often overlooked, despite its significant occurrence. OBJECTIVE: To evaluate the worldwide prevalence of sexual dysfunction among health care workers. METHODS: A comprehensive systematic review and meta-analysis of observational studies ranging from 2003 to 2023 were performed to compile prevalence estimates of sexual dysfunction among health care workers. A random effects model was implemented to amalgamate the prevalence analysis. Study heterogeneity was discerned by I2 and χ2 statistics. To assess potential publication bias, an Egger's test and a funnel plot were employed. RESULTS: This meta-analysis incorporated 39 studies from 16 countries, encompassing 44 017 health care workers. The pooled prevalence of sexual dysfunction among health care workers was 46.79% (95% CI, 38.09%-55.68%), with a slightly higher prevalence of 49.57% (95% CI, 38.18%-61.01%) among clinical health care workers. The most prevalent forms of sexual dysfunction identified were loss of libido (51.26%), erectile dysfunction (36.99%), sexual dissatisfaction (36.90%), pain during intercourse (28.23%), orgasmic disorders (25.13%), low sexual arousal (23.54%), and lubrication disorders (22.62%). Among various health care professions, nurses exhibited the highest prevalence of sexual dysfunction (56.29%), followed by doctors (37.63%) and other health care workers (24.96%). Additionally, female health care workers experienced a higher prevalence of sexual dysfunction (47.61%) as compared with their male counterparts (32.01%). CONCLUSION: This study indicates that nearly half of health care professionals report experiencing sexual dysfunction, with loss of libido being the most common manifestation. Addressing this issue requires a multistakeholder approach.

Multigenerational effects of disperse blue 79 at environmentally relevant concentrations on zebrafish (Danio rerio) fecundity: An integrated approach.

The brominated azo dye (BAD) Disperse Blue (DB79) is a widespread environmental pollutant. The long-term toxicological effects of DB79 and the mechanisms thereof must be understood to allow assessment of the risks of DB79 pollution. A dual-omics approach employing in silico analysis, bioinformatics, and in vitro bioassays was used to investigate the transgenerational (F0-F2) toxicity of DB79 in zebrafish at environmentally relevant concentrations and identify molecular initiating events and key events associated with DB79-induced fertility disorders. Exposure to 500 µg/L DB79 decreased fecundity in the F0 and F1 generations by > 30 % and increased the condition factor of the F1 generation 1.24-fold. PPARα/RXR and PXR ligand binding activation were found to be critical molecular initiating events associated with the decrease in fecundity. Several key events (changes in fatty acid oxidation and uptake, lipoprotein metabolism, and xenobiotic metabolism and transport) involved in lipid dysregulation and xenobiotic disposition were found to be induced by DB79 through bioinformatic annotation using dual-omics data. The biomolecular underpinnings of decreased transgenerational fertility in zebrafish attributable to BAD exposure were elucidated and novel biomolecular targets in the adverse outcome pathway framework were identified. These results will inform future studies and facilitate the development of mitigation strategies.

Efficient and green production of flavone-5-O-glycosides by glycosyltransferases in Escherichia coli.

O-Glycosylflavonoids exhibit diverse biological activities but their low content in plants is difficult to extract and isolate, and chemical synthesis steps are cumbersome, which are harmful to the environment. Therefore, the biosynthesis of O-glycosylflavonoids represents a green and sustainable alternative strategy, with glycosyltransferases playing a crucial role in this process. However, there are few studies on flavone 5-O-glycosyltransferases, which limits the synthesis of rare flavone 5-O glycosides by microorganisms. In this study, we characterized a highly regioselectivity flavone 5-O glycosyltransferase from Panicum hallii. Site-directed mutagenesis at residue P141 switches glucosylation to xylosylation. Using a combinatorial strategy of metabolic engineering, we generated a series of Escherichia coli recombinant strains to biocatalyze glycosylation of the typical flavone apigenin. Ultimately, further optimization of transformation conditions, apigenin-5-O-glucoside and apigenin-5-O-xyloside were biosynthesized for the first time so far, and the yields were 1490 mg/L and 1210 mg/L, respectively. This study provides a biotechnological component for the biosynthesis of flavone-5-O-glycosides, and established a green and sustainable approach for the industrial production of high-value O-glycosylflavones by engineering, which lays a foundation for their further development and application in food and pharmaceutical fields.

Visualizing ClO- fluctuations in drug-induced liver injury and bacterium via a robust ratiometric fluorescent probe.

As a type of reactive oxygen species, hypochlorous acid (ClO-) plays an important role in sterilization, disinfection and protection in organisms. However, excessive production of ClO- is closely related to various diseases. In this work, we have designed a robust ratiometric fluorescent probe, RDB-ClO, using the excited-state intramolecular proton transfer (ESIPT) strategy. RDB-ClO was achieved by modifying 2-(2-(benzo[d]thiazol-2-yl)-6-(diethylamino)-3-oxo-3H-xanthen-9-yl) benzoic acid (RDB-OH) with a 1-naphthoyl chloride group, specifically for the sensitive detection of ClO-. In the presence of ClO-, RDB-ClO demonstrated relatively good performance, showing swift response time (35 s), low detection limit of 5.1 nM and high selectivity towards ClO-. Notably, the convenience and accessibility detection of ClO- has been implemented using test strip and agarose probe. RDB-ClO effectively tracked both endogenous and exogenous ClO- in HeLa cells, HepG2 cells and zebrafish. Additionally, it is successfully applied to detect changes of exogenous ClO- content in E. coli. and acetaminophen (APAP)-induced liver injury in mice. The development of RDB-ClO represents a promising molecular tool for studying the pathogenesis of DILI and biotransformation of ClO- in bacteria.

Clustering-triggered emission mechanism of carboxymethyl ß-cyclodextrin aqueous solution and efficient recognition of Fe3+ in mixed ions.

Most nonconventional luminogens enjoy good water solubility and biocompatibility, showing unique application prospects in fields like biological imaging. Although clustering-triggered emission (CTE) mechanisms have been proposed to explain such emissions, the have not been thoroughly elucidated, which limits their development and application. Here, the photoluminescence properties of carboxymethyl ß-cyclodextrin (CM-ß-CD) aqueous solution are utilized to further investigate the effects of changes in concentration, in order to elucidate the emission mechanism through cryo-transmission electron microscopy (cryo-TEM), small-angle X-ray scattering (SAXS), molecular interaction analysis, and theoretical calculation. The results showed that the size distribution, morphology, and distance between water aggregates were successfully correlated with the cluster emission centers. The emission mechanism of nonconventional luminogen solutions was more clearly and intuitively elucidated, which has a promoting effect on the emission and application of this field. It is interesting that temperature-dependent emission spectra show the blue-shift phenomenon of PL with increasing excitation wavelengths. Moreover, due to its strong static quenching effect for Fe3+, CM-ß-CD can efficiently detect Fe3+ in mixed-ion aqueous solutions. It provides a strategy to clarify the CTE mechanism of nonconventional luminogen solutions more clearly and its application of mixed-ion detection.

Genetic Strategies and Mechanisms for Improving Ribonucleic Acid Levels of Saccharomyces pastorianus.

Developing microorganisms with a high ribonucleic acid (RNA) content is crucial for the RNA industry. Numerous studies have been conducted to enhance RNA production in yeast cells through genetic engineering, yet precise mechanisms remain elusive. Previously, upregulation of TAL1 or PGM2 and deleting PRS5 or DBP8 individually could increase the RNA content in Saccharomyces pastorianus. In this study, within these genetically modified strains, the intracellular nucleotide levels notably increased following cell fragmentation. Deletion of PRS5 and DBP8 within the strain prompted the upregulation of genes sharing similar functions, consequently augmenting the flow of the gene pathway. Furthermore, the upregulation of genes encoding cell-cycle-dependent protein kinases (CDK) was observed in the G03-△PRS5 strain. The influence of TAL1 and PGM2 on RNA content was attributed to the pentose phosphate pathway (PPP). The RNA content of polygenic recombinant strains, G03-△PRS5+△DBP8 and G03-△PRS5+△DBP8+PGM2, displayed the most significant improvement, increasing by 71.8 and 80.1% when compared to the parental strain. Additionally, the maximum specific growth rate of cells increased in these strains. This study contributes valuable insights into the genetic mechanisms underlying high nucleic acid synthesis in S. pastorianus.

The effect of central sleep apnea on sleep architecture in children with obstructive sleep apnea.

OBJECTIVE: This study aimed to investigate how central sleep apnea (CSA) impacts sleep patterns in children with obstructive sleep apnea (OSA). METHODS: Children undergoing polysomnography (PSG) were enrolled and sorted into two groups: those with OSA alone (Group A) and those with both OSA and CSA (CAI <1 nd: children with 10 % CSA or more and less than 50 %, Group B). Statistical analysis was conducted to compare sleep structure and clinical features between Group A and Group B. RESULTS: Group B exhibited significantly higher respiratory events, apnea hypoventilation index, apnea index and oxygen desaturation index (ODI) compared to Group A (p < 0.05). Group B also showed higher total sleep time and arousal index than Group A (P < 0.05). The proportion of time spent in stage N3 was lower in Group B than in Group A (P < 0.05). Moreover, mean heart rate and minimum heart rate were higher in Group B compared to Group A (P < 0.05).Minimum oxygenation levels (including non-rapid eye movement (NREM) stages) were lowe in Group B than in Group A (P < 0.05). Additionally, the prevalence of positional obstructive sleep apnea (P-OSA) was greater in Group B than in Group A (P < 0.05). CONCLUSION: In comparison to those with OSA alone, children with OSA and concurrent CSA exhibited distinct sleep patterns, including reduced N3uration, higher arousal index, longer respiratory events, higher ODI, and lower oxygen saturation, higher heart rate.

Low concentrations of tetrabromobisphenol A promote the biofilm formation of methicillin-resistant Staphylococcus aureus.

The effect and underlying mechanism of tetrabromobisphenol A (TBBPA), a plastic additive, on biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA USA300) remain unknown. This study first investigated the impact of different concentrations of TBBPA on the growth and biofilm formation of USA300. The results indicated that a low concentration (0.5 mg/L) of TBBPA promoted the growth and biofilm formation of USA300, whereas high concentrations (5 mg/L and 10 mg/L) of TBBPA had inhibitory effects. Further exploration revealed that the low concentration of TBBPA enhance biofilm formation by promoting the synthesis of extracellular proteins, release of extracellular DNA (eDNA), and production of staphyloxanthin. RTqPCR analysis demonstrated that the low concentration of TBBPA upregulated genes associated with extracellular protein synthesis (sarA, fnbA, fnbB, aur) and eDNA formation (atlA) and increased the expression of genes involved in staphyloxanthin biosynthesis (crtM), suggesting a potential mechanism for enhanced resistance of USA300 to adverse conditions. These findings shed light on how low concentrations of TBBPA facilitate biofilm formation in USA300 and highlight the indirect impact of plastic additives on pathogenic bacteria in terms of human health. In the future, in-depth studies about effects of plastic additives on pathogenicity of pathogenic bacteria should be conducted. CAPSULE: The protein and eDNA contents in biofilms of methicillin-resistant Staphylococcus aureus are increased by low concentrations of TBBPA.

Deciphering microbial metabolic interactions and their implications for community dynamics in acid mine drainage sediments.

The microbially-mediated reduction processes have potential for the bioremediation of acid mine drainage (AMD), which represents a worldwide environment problem. However, we know little about the microbial interactions in anaerobic AMD sediments. Here we utilized genome-resolved metagenomics to uncover the nature of cooperative and competitive metabolic interactions in 90 AMD sediments across Southern China. Our analyses recovered well-represented prokaryotic communities through the reconstruction of 2625 population genomes. Functional analyses of these genomes revealed extensive metabolic handoffs which occurred more frequently in nitrogen metabolism than in sulfur metabolism, as well as stable functional redundancy across sediments resulting from populations with low genomic relatedness. Genome-scale metabolic modeling showed that metabolic competition promoted microbial co-occurrence relationships, suggesting that community assembly was dominated by habitat filtering in sediments. Notably, communities colonizing more extreme conditions tended to be highly competitive, which was typically accompanied with increased network complexity but decreased stability of the microbiome. Finally, our results demonstrated that heterotrophic Thermoplasmatota associated with ferric iron and sulfate reduction contributed most to the elevated levels of competition. Our study shed light on the cooperative and competitive metabolisms of microbiome in the hazardous AMD sediments, which may provide preliminary clues for the AMD bioremediation in the future.

Multiportal Arthroscopy-assisted Surgical Resection of Diffuse-type Tenosynovial Giant Cell Tumors in the Ankle Joint Yields Favorable Clinical Outcomes: A Retrospective Study.

OBJECTIVE: Diffuse-type tenosynovial giant cell tumors (Dt-TGCTs) commonly occur in the knee joint and tend to recur postoperatively. However, limited clinical data are available on ankle joint involvement especially associated multiportal arthroscopic treatment outcomes. The purpose of this study was to report the clinical results of multiportal arthroscopy-assisted resection of Dt-TGCTs of the ankle. METHODS: We retrospectively reviewed the clinical data of 33 patients with Dt-TGCT of the ankle who underwent multiportal arthroscopic treatment between August 2011 and December 2020. Clinical follow-up included the visual analogue scale (VAS) score, American Orthopedic Foot and Ankle Society (AOFAS) score, Kofoed score, and recurrence rate to assess surgical outcomes. The number of patients who achieved the patient acceptable symptom state (PASS) based on the AOFAS score was also examined. Additionally, the patients were categorized into two groups based on the final surgical approach: Group A who underwent multiportal arthroscopic synovectomy and Group AO who underwent combined arthroscopic and open surgical excision. Intergroup comparisons were conducted. Intraoperative characteristics, such as the number of patients with involvement of the tarsal tunnel and fibularis tendon and the Outerbridge grading of cartilage damage, were recorded to assess the selection of surgical procedures. RESULTS: Among the 33 patients, 15 were assigned to Group A, and 18 were in Group AO. The median follow-up duration for the 33 patients was 77 months (range, 28-142 months). The median VAS score was 1 (range, 0-4), the AOFAS score was 96 (range, 65-100), and the Kofoed score was 96 (range, 67-100). A total of 27 patients (82%) achieved PASS based on AOFAS scores, while five patients (15%) had recurrence. No statistically significant difference was observed between the two groups in recurrence rate, follow-up VAS score, AOFAS score, Kofoed score, or number of patients who reached the PASS (p > 0.05). In the AO group, 16 cases of Dt-TGCT involved the tarsal tunnel, and 11 cases involved the fibularis tendon. All these patients exhibited extension beyond the joint. In contrast, only one patient in Group A had involvement of the tarsal tunnel. Statistically significant differences were observed between the groups (p < 0.001). CONCLUSION: This study demonstrated that, with the assistance of a multiportal arthroscopic approach, surgical excision of Dt-TGCT in the ankle resulted in favorable clinical outcomes with a relatively low recurrence rate. Additionally, patients with extra-articular involvement were more likely to require concomitant open surgery.

Carrier-free nanoparticles based on self-assembly of 5-FU and copper-genistein complexes for the combined treatment of hepatocellular carcinoma.

5-Fluorouracil (5-FU) is commonly used as a chemotherapeutic drug for advanced HCC. However, the effectiveness of 5-FU is limited by the emergence of resistance and poor targeting efficiency. Combining 5-FU with natural compounds has shown promise in HCC treatment. In this study, we prepared carrier-free nanoparticles (GEN-Cu-GEN@FUA) containing 5-FU and genistein (GEN) in a synergistic ratio via a green synthesis procedure. The resulting GEN-Cu-GEN@FUA nanoparticles had a spherical or near spherical shape, a dynamic size of 129.3 ± 40.1 nm, and a high drug loading content of approximately 21.40% (5-FU) and 61.48% (GEN). These nanoparticles exhibited approximately 3.6-fold lower IC50 value than 5-FU alone in Bel-7402 cells and resulted in a 3.7-fold greater reduction in tumor weight compared to 5-FU alone in Bel-7402 tumor-bearing BALB/c mice. Importantly, the nanoparticles showed negligible systemic toxicity due to their synergistic effect on cancer cell dysfunction and significant amplification of intracellular glutathione consumption. Our findings suggest that the developed carrier-free nanomedicines offer a highly promising platform for the co-delivery of genistein (GEN) copper(II) complexes and 5-FU, with easy fabrication and great potential for clinical translation in HCC synergistic therapy.

Forecasting and analyzing influenza activity in Hebei Province, China, using a CNN-LSTM hybrid model.

BACKGROUND: Influenza, an acute infectious respiratory disease, presents a significant global health challenge. Accurate prediction of influenza activity is crucial for reducing its impact. Therefore, this study seeks to develop a hybrid Convolution Neural Network-Long Short Term Memory neural network (CNN-LSTM) model to forecast the percentage of influenza-like-illness (ILI) rate in Hebei Province, China. The aim is to provide more precise guidance for influenza prevention and control measures. METHODS: Using ILI% data from 28 national sentinel hospitals in the Hebei Province, spanning from 2010 to 2022, we employed the Python deep learning framework PyTorch to develop the CNN-LSTM model. Additionally, we utilized R and Python to develop four other models commonly used for predicting infectious diseases. After constructing the models, we employed these models to make retrospective predictions, and compared each model's prediction performance using mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE), and other evaluation metrics. RESULTS: Based on historical ILI% data from 28 national sentinel hospitals in Hebei Province, the Seasonal Auto-Regressive Indagate Moving Average (SARIMA), Extreme Gradient Boosting (XGBoost), Convolution Neural Network (CNN), Long Short Term Memory neural network (LSTM) models were constructed. On the testing set, all models effectively predicted the ILI% trends. Subsequently, these models were used to forecast over different time spans. Across various forecasting periods, the CNN-LSTM model demonstrated the best predictive performance, followed by the XGBoost model, LSTM model, CNN model, and SARIMA model, which exhibited the least favorable performance. CONCLUSION: The hybrid CNN-LSTM model had better prediction performances than the SARIMA model, CNN model, LSTM model, and XGBoost model. This hybrid model could provide more accurate influenza activity projections in the Hebei Province.

Spatial variation, emissions, transport, and risk assessment of organophosphate esters in two large petrochemical complexes in southern China.

Organophosphate esters (OPEs) serve as significant flame retardants and plasticizers in various petrochemical downstream products. The petrochemical industry could be a potential source of atmospheric OPEs, but their emissions from this industry are poorly understood. The present study revealed the spatial variation, emission, and atmospheric transport of traditional and novel OPEs (TOPEs and NOPEs, respectively) in atmospheric particulate matter (PM) across Hainan and Guangdong petrochemical complexes (HNPC and GDPC, respectively) in southern China. The total concentrations of TOPEs ranged from 232 to 46,002 pg/m3 and from 200 to 20,347 pg/m3 in the HNPC and GDPC, respectively, which were substantially higher than those of NOPEs (HNPC: 23.5-147 pg/m3, GDPC: 13.9-465 pg/m3). Enterprises involved in the production of downstream petrochemical products presented relatively high concentrations of OPEs, indicating evident emissions of these pollutants in the petrochemical industry. The correlations of PM-bound OPEs in the atmosphere are determined mainly by their coaddition to industrial products or their coexistence in technical mixtures. The annual emissions of TOPEs and NOPEs in the HNPC were 42.6 kg and 0.34 kg, respectively, and those in the GDPC were 116 kg and 1.85 kg, respectively. OPEs from the HNPC can reach Vietnam, Cambodia, and Guangxi Province, China, and those from the GDPC can reach Guangxi Province and Hunan Province via atmospheric transmission after 24 h of emission. The OPE concentrations reaching the receptor regions were generally less than 3.20 pg/m3. Risk assessment revealed that OPE inhalation exposure on two petrochemical complexes likely poses minor risks for people living in the study areas, but the risk resulting from two chlorinated OPEs should be noted since they are close to the threshold values. This study has implications for enhancing control measures for OPE emissions to reduce health risks related to the petrochemical industry.

Potassium voltage-gated channel subfamily H member 2 (KCNH2) is a promising target for incretin secretagogue therapies.

Derived from enteroendocrine cells (EECs), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are pivotal incretin hormones crucial for blood glucose regulation. Medications of GLP-1 analogs and GLP-1 receptor activators are extensively used in the treatment of type 2 diabetes (T2D) and obesity. However, there are currently no agents to stimulate endogenous incretin secretion. Here, we find the pivotal role of KCNH2 potassium channels in the regulation of incretin secretion. Co-localization of KCNH2 with incretin-secreting EECs in the intestinal epithelium of rodents highlights its significance. Gut epithelial cell-specific KCNH2 knockout in mice improves glucose tolerance and increases oral glucose-triggered GLP-1 and GIP secretion, particularly GIP. Furthermore, KCNH2-deficient primary intestinal epithelial cells exhibit heightened incretin, especially GIP secretion upon nutrient stimulation. Mechanistically, KCNH2 knockdown in EECs leads to reduced K+ currents, prolonged action potential duration, and elevated intracellular calcium levels. Finally, we found that dofetilide, a KCNH2-specific inhibitor, could promote incretin secretion in enteroendocrine STC-1 cells in vitro and in hyperglycemic mice in vivo. These findings elucidate, for the first time, the mechanism and application of KCNH2 in regulating incretin secretion by EECs. Given the therapeutic promise of GLP-1 and GIP in diabetes and obesity management, this study advances our understanding of incretin regulation, paving the way for potential incretin secretagogue therapies in the treatment of diabetes and obesity.